title: Recognition of iodixanol by dendritic cells increases the cellular response in delayed allergic reactions to contrast media.
abstract: BACKGROUND
  Delayed reactions to iodine contrast media (CM) account for 1-3% of patients with adverse reactions to iodine CM. The cellular and molecular mechanisms of these reactions remain poorly documented. Although most of these reactions are T cell mediated, the involvement of dendritic cells (DC) has not been investigated sufficiently.
  
  
  OBJECTIVE
  To determine whether the T cell response to iodixanol requires DC as antigen-presenting cell and, more particularly, to evaluate the changes induced by iodixanol on DC maturation and in vitro production of cytokines after drug stimulation in patients with maculopapular exanthema.
  
  
  METHODS
  Peripheral blood lymphocytes, immature monocyte-derived DC (imDC) and skin biopsies were obtained from patients with delayed reactions to iodixanol and tolerant subjects. We studied the consequences of the interaction between DC, lymphocytes and iodixanol by phenotype analysis, proliferation and cytokine production.
  
  
  RESULTS
  A T-cell-mediated reaction was evidenced in patient biopsies, with a lymphocyte-rich, peri-vascular infiltrate. Iodixanol induced maturation of imDC from patients but not from controls, with expression of the co-stimulatory markers CD83, CD86 and CD40 and an increase in mean fluorescence intensity of CD80, CD86 and HLA-DR. In the absence of DC, positive cell proliferation to iodixanol was detected in only one patient while the addition of DC produced a positive test in five of the six patients. Similarly, the increase in cytokines (IFN-γ, IL-2, IL-6, IL-1b and TNF-α) was higher when imDC were introduced into the culture together with the culprit drug.
  
  
  CONCLUSIONS
  These results provide evidence for a DC-mediated mechanism in delayed allergic reactions to CM, influencing T cell proliferation and cytokine production. These new insights will be helpful for designing immunotherapeutic strategies and in vitro diagnostic tests of CM-delayed reactions.
authors.affiliation: INSERM U-954, Nutrition-Génétique et exposition aux risques environnmentaux, Faculty of Medicine, University Henry Poincaré, Nancy, France.
authors.forename: C
authors.initials: C
authors.lastname: Antunez
authors.forename: A
authors.initials: A
authors.lastname: Barbaud
authors.forename: E
authors.initials: E
authors.lastname: Gomez
authors.forename: S
authors.initials: S
authors.lastname: Audonnet
authors.forename: S
authors.initials: S
authors.lastname: Lopez
authors.forename: R-M
authors.initials: RM
authors.lastname: Guéant-Rodriguez
authors.forename: I
authors.initials: I
authors.lastname: Aimone-Gastin
authors.forename: F
authors.initials: F
authors.lastname: Gomez
authors.forename: M
authors.initials: M
authors.lastname: Blanca
authors.forename: J-L
authors.initials: JL
authors.lastname: Guéant
mesh_terms: D000369:Aged, 80 and over; D049109:Cell Proliferation / Q000187:drug effects; D003287:Contrast Media / Q000009:adverse effects*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000175:diagnosis / Q000276:immunology*; D017613:Iodine Compounds / Q000009:adverse effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity; D012882:Skin Tests; D014283:Triiodobenzoic Acids / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D003287:Contrast Media; D016207:Cytokines; D017613:Iodine Compounds; D014283:Triiodobenzoic Acids; C044834:iodixanol